The life expectancy of patients with diabetes has been significantly expanded; however, along with this increased life expectancy has come an increased incidence of complications and morbidity. Much of the morbidity is associated with microvascular complications with diabetic retinopathy (DR) being the most prevalent. DR is caused by inappropriate activation of vasculogenesis and angiogenesis in the vessels of the retina. There is a genetic link for susceptibility to the development of DR based on familial aggregation studies. This study will investigate candidate genes whose products are known to have a function in microvasculature maintenance and formation utilizing a well characterized type 1 diabetic population with length of disease of at least 25 years to address the three aims of this project: 1) identifying gene(s) involved with susceptibility to diabetic retinopathy, 2) identifying genes involved with severity of diabetic retinopathy attained, and 3) identifying genes involved with length of diabetic retinopathy free type 1 diabetes. This investigation has the potential to illucidate mechanisms involved with the development of diabetic retinopathy, which may improve identification of at risk individuals as well as open additional avenues for therapy including preventive therapies. [unreadable] [unreadable]